Essential hypertension causes severe complications such as apoplexy, ischemic heart diseases and nephrosclerosis. These complications are fundamentally associated with vascular disorders by excessive proliferation of vascular smooth muscle cells (VSMC), and are the targets of the treatment of hypertension. We have already shown the enhanced expression of platelet-derived growth factor (PDGF) A-chain mRNA in spontaneous hypertensive rat (SHR)-derived VSMC (Fukuda N, Kubo A, Watanabe Y, Nakayama T, Soma M, Izumi Y, Kanmatsuse K. (1997) J. Hypertens. 15:1123., Fukuda N, Kishioka H, Satoh C, Nakayama T, Watanabe Y, Soma M, Izumi Y, Kanmatsuse K. (1997) Am. J. Hypertens. 10:1117). On the other hand, restenosis of coronary arteries takes place in about 40 percent after percutaneous transluminal coronary angioplasty (PTCA) as a treatment of myocardial infarction, and there is no effective pharmacotherapy for the restenosis at present, posing a serious problem in the field of cardiovascular diseases. Histopathologically, it is known that PDGF A-chain is involved in the migration of medial smooth muscle cells and the neointimal formation by the proliferation of (Scott N A, Cipolla G D, Ross C E, Dunn B, Martin F H, Simonet L, Wilcox J N. (1996) Circulation 93:2178).
It is thought that the cell growth can be blocked by various manners. One of them is to control the expression of growth factors including PDGF. PDGF is a potent stimulator of VSMC proliferation which displays proliferative action and migratory action to the cell growth. PDGF is a dimer protein composed of disulfide-bound polypeptides known as the A-chain and the B-chain. Three forms (AA, AB, and BB) of PDGF differ in cell distribution and biological activity, and selectively interact with at least two PDGF receptors (αand β). Stiko-Rahm et al. have shown that although cultivated VSMC or VSMC in atherosclerotic plaque expresses PDGF A-chain mRNA and secretes PDGF-AA protein, but growth-arrested normal VSMC do not express PDGF A-chain mRNA (Stiko-Rahm A, Hultgardh-Nillsson A, Regnstrom J, Hamsten A, Nilsson J. (1992) Arterioscler Thromb 12:1099).